Studies planned will examine, in the developing rat, the physical state of circulating thyroxine, its rates of peripheral uptake and utilization, its feedback effects upon the hypothalamus and pituitary, the role of the hypothalamus and adjacent areas in the regulation of pituitary-thyroid activity, TRH synthesis by the hypothalamus, and the effects of possible neural mediators upon TRH release. Information obtained will contribute to the eventual construction of a comprehension model describing CNS-pituitary-thyroid functions during maturation. Types and maximum binding capacities of thyroxine-binding proteins will be determined by electrophoretic methods in fetal, infant and adult plasma, and free and bound circulating thyroxine by a radioimmunoassay method. Thyroxine utilization by liver, muscle and kidney at various ages will be examined in vitro and the metabolic products identified chromatographically. Following cuts in various parts of the hypothalamus with the Halasz-type knife and after bilateral electrolytic lesions in the preoptic area of infants, thyroid growth and 125I and 99MTc metabolism will be measured with and without goitrogen feeding. Changes in circulating TSH (radioimmunoassay) will be examined in infants during in vivo infusion of TRH, with and without thyroxine pretreatment. Fragments of fetal, infant and adult hypothalami will be incubated to determine (1) rates of incorporation of labelled amino acids into TRH(isolated either chromatographically or by anti-TRH antibody), (2) effects of thyroxine pretreatment upon TRH synthesis and release, and (3) TRH release in response to possible neural mediators.